Comparative Effectiveness of Field-Treatments for Multiple Actinic

描述(申请人提供)：非黑色素瘤皮肤癌(NMSCs)是美国最常见的癌症，每年诊断超过200万例。尽管有大量的人受到影响并由此造成疾病负担，但还没有确定有效的化学预防策略，特别是在阳光损伤的人中，他们存在癌前皮损，患皮肤癌的风险很高。光化性角化病(AKs)是一种癌前病变，发生在阳光损伤的皮肤上，可进展为NMSCs。治疗多发性白血病最常用的两种外用药物是5-氟尿嘧啶(5-FU)和咪喹莫特。尽管在美国，AK的就诊人数每年超过370万人次，他们的治疗给我们的医疗系统带来了巨大的财政负担，每年花费超过10亿美元，但还没有研究比较这两种局部实地疗法的有效性。我们建议比较5-FU和咪喹莫特在预防NMSCs(主要目的)和AKS(次要目的)方面的有效性，使用北加州凯撒永久(KPNC)的回顾性数据。我们还试图确定每种药物在5年随访期内的剂量-反应曲线。该项目的一个独特特点是背景，它允许在现实世界的实践环境中确定有效性。KPNC还提供了丰富的电子数据库的额外优势，具有丰富的暴露信息(详细的药房数据库)、结果信息(唯一的NMSC登记，确定了不可报告的皮肤癌)，以及潜在的相关协变量。这项建议的另一个独特之处是处理回溯性观察数据的方式，利用新的生物统计学方法(点处理边缘结构模型)得出关于暴露与结果之间的关系的随意推论，这将在临床试验环境中获得。这些新开发的方法以前从未在皮肤流行病学中使用过。该项目的目标与NIAMS的长期规划目标相一致，即通过执行“皮肤病治疗的治疗和联合治疗方法的比较有效性”来增加与皮肤相关的临床研究。通过实现我们的研究目标，我们可以帮助在高危人群中找到预防美国最常见癌症的最有效的局部制剂。

DESCRIPTION (provided by applicant): Non-melanoma skin cancer (NMSCs) is the most common cancer in America, with over 2 million cases diagnosed annually. Despite the large population affected and resultant burden of disease, no effective chemopreventative strategies have been identified, especially among sun-damaged individuals with existing precancerous skin lesions who are at high risk of developing skin cancer. Actinic keratoses (AKs) are precancerous skin lesions that arise on sun-damaged skin and can progress to NMSCs. The two most widely used topical agents for the treatment of multiple AKs are 5- fluorouracil (5-FU) and imiquimod. Although visits for AKs accounts for over 3.7 million ambulatory care office visits per year in the US and their treatment poses a substantial financial burden to our healthcare system, costing over a billion dollars annually, no studies have compared the effectiveness of the these twp topical field-based therapies. We propose to compare the effectiveness of 5-FU and imiquimod in preventing NMSCs (primary aim) and AKs (secondary aim) using retrospective data from Kaiser Permanente Northern California (KPNC). We also seek to ascertain dose-response curves for each drug over a 5 year follow-up period. One of the unique features of the project is the setting, which allows for ascertainment of effectiveness in a real-world practice environment. KPNC also offers the added advantage of rich electronic databases, with a wealth of information of exposure (detailed pharmacy database), outcome (unique NMSC registry which identified non-reportable skin cancer), and potentially relevant co-variates. The other unique aspect of this proposal is the way in which the retrospective observational data is approached, utilizing novel biostatistical methodologies (point-treatment marginal structural models) to draw casual inference regarding the relationship between exposure and outcome as would be obtained in a clinical trial setting. These newly developed methods have not been previously used in Dermato-epidemiology. The goals of this project align with NIAMS's long-range planning goals of increasing skin related clinical research by performing "comparative effectiveness of therapies, and combination therapy approaches for skin disease treatment." By accomplishing our study aims, we can help identify the most effective topical agent among high risk individuals for the prevention of the most common cancer in America.